Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27364 | 82315;82316;82317 | chr2:178564042;178564041;178564040 | chr2:179428769;179428768;179428767 |
| N2AB | 25723 | 77392;77393;77394 | chr2:178564042;178564041;178564040 | chr2:179428769;179428768;179428767 |
| N2A | 24796 | 74611;74612;74613 | chr2:178564042;178564041;178564040 | chr2:179428769;179428768;179428767 |
| N2B | 18299 | 55120;55121;55122 | chr2:178564042;178564041;178564040 | chr2:179428769;179428768;179428767 |
| Novex-1 | 18424 | 55495;55496;55497 | chr2:178564042;178564041;178564040 | chr2:179428769;179428768;179428767 |
| Novex-2 | 18491 | 55696;55697;55698 | chr2:178564042;178564041;178564040 | chr2:179428769;179428768;179428767 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs981687121  |
None | 0.025 | N | 0.353 | 0.332 | 0.469742815239 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs981687121 |
None | 0.025 | N | 0.353 | 0.332 | 0.469742815239 | gnomAD-4.0.0 | 3.71831E-06 | None | None | None | None | N | None | 8.00983E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs375407842 |
-0.355 | 0.099 | N | 0.292 | 0.254 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| V/I | rs375407842 |
-0.355 | 0.099 | N | 0.292 | 0.254 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/I | rs375407842 |
-0.355 | 0.099 | N | 0.292 | 0.254 | None | gnomAD-4.0.0 | 8.9682E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.67525E-05 | 0 | 0 |
| V/L | rs375407842 |
-0.357 | 0.63 | N | 0.621 | 0.186 | 0.337868961071 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 0 | 0 |
| V/L | rs375407842 |
-0.357 | 0.63 | N | 0.621 | 0.186 | 0.337868961071 | gnomAD-4.0.0 | 1.59133E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88239E-05 | 0 | 0 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.8199 | likely_pathogenic | 0.822 | pathogenic | -1.923 | Destabilizing | 0.025 | N | 0.353 | neutral | N | 0.494972633 | None | None | N |
| V/C | 0.9414 | likely_pathogenic | 0.9399 | pathogenic | -1.437 | Destabilizing | 0.997 | D | 0.766 | deleterious | None | None | None | None | N |
| V/D | 0.9988 | likely_pathogenic | 0.9991 | pathogenic | -2.547 | Highly Destabilizing | 0.987 | D | 0.845 | deleterious | None | None | None | None | N |
| V/E | 0.9956 | likely_pathogenic | 0.9965 | pathogenic | -2.25 | Highly Destabilizing | 0.967 | D | 0.819 | deleterious | D | 0.524940172 | None | None | N |
| V/F | 0.794 | likely_pathogenic | 0.8471 | pathogenic | -1.083 | Destabilizing | 0.987 | D | 0.777 | deleterious | None | None | None | None | N |
| V/G | 0.9301 | likely_pathogenic | 0.9296 | pathogenic | -2.539 | Highly Destabilizing | 0.935 | D | 0.824 | deleterious | D | 0.524940172 | None | None | N |
| V/H | 0.998 | likely_pathogenic | 0.9986 | pathogenic | -2.45 | Highly Destabilizing | 0.999 | D | 0.815 | deleterious | None | None | None | None | N |
| V/I | 0.0943 | likely_benign | 0.1069 | benign | -0.167 | Destabilizing | 0.099 | N | 0.292 | neutral | N | 0.47074863 | None | None | N |
| V/K | 0.9954 | likely_pathogenic | 0.9963 | pathogenic | -1.592 | Destabilizing | 0.975 | D | 0.813 | deleterious | None | None | None | None | N |
| V/L | 0.4418 | ambiguous | 0.4975 | ambiguous | -0.167 | Destabilizing | 0.63 | D | 0.621 | neutral | N | 0.47214264 | None | None | N |
| V/M | 0.5476 | ambiguous | 0.6204 | pathogenic | -0.305 | Destabilizing | 0.987 | D | 0.715 | prob.delet. | None | None | None | None | N |
| V/N | 0.9937 | likely_pathogenic | 0.995 | pathogenic | -2.149 | Highly Destabilizing | 0.987 | D | 0.824 | deleterious | None | None | None | None | N |
| V/P | 0.995 | likely_pathogenic | 0.9959 | pathogenic | -0.727 | Destabilizing | 0.987 | D | 0.815 | deleterious | None | None | None | None | N |
| V/Q | 0.9932 | likely_pathogenic | 0.9948 | pathogenic | -1.816 | Destabilizing | 0.987 | D | 0.811 | deleterious | None | None | None | None | N |
| V/R | 0.9908 | likely_pathogenic | 0.9926 | pathogenic | -1.709 | Destabilizing | 0.987 | D | 0.816 | deleterious | None | None | None | None | N |
| V/S | 0.97 | likely_pathogenic | 0.9736 | pathogenic | -2.773 | Highly Destabilizing | 0.95 | D | 0.81 | deleterious | None | None | None | None | N |
| V/T | 0.8915 | likely_pathogenic | 0.9011 | pathogenic | -2.302 | Highly Destabilizing | 0.916 | D | 0.659 | neutral | None | None | None | None | N |
| V/W | 0.9975 | likely_pathogenic | 0.9986 | pathogenic | -1.657 | Destabilizing | 0.999 | D | 0.801 | deleterious | None | None | None | None | N |
| V/Y | 0.9892 | likely_pathogenic | 0.9923 | pathogenic | -1.218 | Destabilizing | 0.996 | D | 0.757 | deleterious | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.